The long-term objective of this project is to develop electrophilic and photoaffinity ligands for opioid receptors which may be useful in the characterization and/or purification of these receptors. In addition, the compounds may provide long-acting agonists or antagonists. Electrophilic and photoactivatable groups are attached to ligands known to be bound to mu-, kappa-, or delta-opioid receptor subtypes. The compounds would be employed principally as pharmacological tools to aid in characterization of receptor subtypes. The compounds to be prepared are: 1. mu-Antagonists and agonists derived primarily from naltrexone, and less from oxymorphone, in which the electrophilic groups and photoaffinity probes are attached to the 6-, 7-, 8-positions. The major focus of this application is on mu-opioid receptor ligands. 2. Possible electrophilic and photoaffinity probes derived from the selective delta-antagonist naltrindole. 3. Possible electrophilic and photoaffinity probes of selective kappa- antagonist norbinaltorphimine and kappa-agonist ICI-199441. All compounds will be tested in opioid receptor binding assays for selectivity at mu-, kappa-, and delta-subclasses of opioid receptors. Active compounds with high affinity will also be tested for possible irreversible effects. Electrophiles will be preincubated and possible photoaffinity probes will be also be photolyzed. The binding assay will be repeated to determine is there is irreversible binding. Compounds with interesting activities will also be submitted to CPDD for testing in vivo.